Heparin promotes cardiac differentiation of human pluripotent stem cells in chemically defined albumin-free medium, enabling consistent manufacture of cardiomyocytes

Yongshun Lin, Kaari L. Linask, Barbara Mallon, Kory Johnson, Michael Klein, Jeanette Beers, Wen Xie, Yubin Du, Chengyu Liu, Yinzhi Lai, Jizhong Zou, Mark Haigney, Hushan Yang, Mahendra Rao, Guokai Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Cardiomyocytes can be differentiated from human pluripotent stem cells (hPSCs) in defined conditions, but efficient and consistent cardiomyocyte differentiation often requires expensive reagents such as B27 supplement or recombinant albumin. Using a chemically defined albumin-free (E8 basal) medium, we identified heparin as a novel factor that significantly promotes cardiomyocyte differentiation efficiency, and developed an efficient method to differentiate hPSCs into cardiomyocytes. The treatment with heparin helped cardiomyocyte differentiation consistently reach at least 80% purity (up to 95%) from more than 10 different hPSC lines in chemically defined Dulbecco’s modified Eagle’s medium/F-12-based medium on either Matrigel or defined matrices like vitronectin and Synthemax. One of heparin’s main functions was to act as a Wnt modulator that helped promote robust and consistent cardiomyocyte production. Our study provides an efficient, reliable, and cost-effective method for cardiomyocyte derivation from hPSCs that can be used for potential large-scale drug screening, disease modeling, and future cellular therapies.

Original languageEnglish
Pages (from-to)527-538
Number of pages12
JournalStem Cells Translational Medicine
Volume6
Issue number2
DOIs
StatePublished - Feb 2017
Externally publishedYes

Keywords

  • Cardiac
  • Cell culture
  • Embryonic stem cells
  • Heparin
  • Induced pluripotent stem cells

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